1,2-Difluoroethylene (HFO-1132): synthesis and chemistry

This article provides a comprehensive overview of the synthesis and chemistry of 1,2-difluoroethylene (HFO-1132). The major routes for the preparation of the E- and Z-isomer of HFO-1132 are reviewed, along with the chemistry in radical, nucleophilic, and electrophilic reactions.


Introduction
In the 1930s, halogenated chlorofluorocarbons (CFCs) and hydrochlorofluorocarbons (HCFCs) were synthesized and have been shown to have low toxicity, which has opened the door for the application as safe refrigerants [1,2].The development of the commercial synthesis of CFCs and HCFCs, along with new refrigeration systems in the 1930s-1960s, has led to the wide application of these materials in household and commercial refrigeration systems [1,2].In addition, CFCs have found applications as propellants, foam-blowing agents, cleaning solvents, etc.Although these groups of fluorinated materials are nonflammable and have low toxicity, CFCs were found to be destructive to the ozone layer of the stratosphere [1,2] due to high ozone-depleting potential (ODP).This has led to the phasing out of CFCs and the replacement with hydrofluorocarbons (HFCs), which show no significant impact on stratospheric ozone [1][2][3].However, as it was demonstrated in the 1980s, HFCs have significant global warming potential (GWP) [1][2][3].In the 2000s, a new generation of refrigerants, namely hydrofluoroolefins (HFOs), which have a short atmospheric lifetime and low GWP [4,5], has been introduced into commercial use [1][2][3].Recently, these compounds and blends thereof have replaced HFCs in refrigerants and air-conditioning systems [1][2][3].
Despite the fact that HFO-1132 has been known for a long time, there are no publications that summarize the chemistry of the compound.With this in mind, the main methods for the preparation of (E/Z)-1,2-difluoroethylene are discussed in this Review article.Special attention is given to the role of 1,2-difluoroethylene in multiple reaction types.

Review Preparation of HFO-1132
In scientific literature, the number of publications on the synthesis of 1,2-difluoroethylene is limited.HFO-1132 was first obtained in 1955 as a byproduct in the reaction of diborane with tetrafluoroethylene [45].To the best of our knowledge, the first preparative route to 1,2-difluoroethylene was described in 1957 by Haszeldine and Steele [46], using trifluoroethylene as starting material (Scheme 1) [46,47].
Consequently, two methods to prepare 1,2-difluoroethylene in the laboratory have been described to date.Even though at least five approaches to HFO-1132 can be found in patent literature, it is not clear which of these can be used for the commercial production of HFO-1132.
The authors of reference [47] explained the higher stability of (Z)-HFO-1132 as follows: Within the family of 1,2-dihaloethylenes, when going from diiodo-and dibromo-to dichloro-and difluoroethylene, the radius of the halogen atom decreases while the electronegativity increases.As a result, the influence of halogen atom electronegativity on the double bond is more significant in 1,2-difluoroethylene, and the relative energy of the cis-isomer decreases, i.e., the cis-isomer of 1,2-difluoroethylene is thermodynamically favored [47].

Deuteration
The stereospecific reaction of (E/Z)-1,2-difluoroethylene with a 1-2 M solution of NaOD in D 2 O (90-120 °C, 2 d) led to the formation of CDF=CDF with high isotopic purity (Scheme 8) [76,77].Additionally, when the reaction was performed using DMSO-d 6 (or CD 3 CN) and CH 3 ONa, H/D exchange occurred already at ambient temperature (25 °C, 20 h) [78].The formation of CDF=CDF was confirmed by NMR spectroscopy, namely by the change of signal multiplicity in the 19 F NMR spectra of Eand Z-isomers of 1,2-difluoroethylene and the disappearance of vinyl protons resonances in the 1 H NMR spectra [78].
An interesting feature of this reaction is the high stereospecificity.In almost all cases, the addition proceeded syn-specific, yielding the erythro-isomer from cis-and the threo-isomer from trans-1,2-difluoroethylene, respectively, with one exception: threo-isomer formation from cis-1,2-difluoroethylene (entry 1, Table 3).Supposedly this was due to dominant steric factors, such that the reaction occurred as anti-addition.a Chloroperoxytrifluoromethane is an unstable compound that decomposed to CF 3 OCl.Therefore, CF 3 OCFH-CFHCl byproduct was also isolated in 11% yield in this reaction.

Addition of N-halo compounds: It was shown by Haszeldine
and Tipping that N-bromobis(trifluoromethyl)amine easily reacted with (Z)-1,2-difluoroethylene to form the addition product in high yield (Scheme 11) [89].However, the stereochemistry of this reaction has not been reported.
A similar reaction of (Z)-1,2-difluoroethylene with N-chloroimidobis(sulfonyl fluoride) (Scheme 12) [90] was shown to be stereounspecific, although the addition product was reported to form in high yield.
In the same publication [90], it was mentioned that (FSO 2 ) 2 NH did not form an addition product in the reaction with (Z)-1,2-difluoroethylene, although the reaction of (FSO 2 ) 2 NH with other olefins, including fluorinated ones, occurred similar to HF addition [90].

Miscellaneous additions:
In reference [91], the addition of trichlorosilane to 1,2-difluoroethylene (Scheme 13) was reported by the Haszeldine group.The reaction under UV irradiation produced the corresponding trichlorosilane in 85% yield, and the silane that was obtained was pyrolyzed to form vinyl fluoride.
It was shown that SF 5 Br easily reacted with the E-and Z-isomer, respectively, of 1,2-difluoroethylene in the presence or absence of light, yielding a mixture of erythro-and threoisomeric addition products in both cases (Scheme 14) [92].However, under light irradiation, conversion and product yield were higher, although the ratio of diastereomers produced in both cases was almost the same for the E-and Z-isomer, respectively, and did not depend on irradiation.
The reaction of 1,2-difluoroethylene with PCl 3 and O 2 was described by Boyce and co-workers [93].Therein, a mixture of products, with diethyl 2-chloro-1,2-difluoroethylphosphonate as main compound, was formed (Scheme 15).This mixture was reacted with absolute ethanol, and the esters formed were separated by distillation and characterized.The authors did not point out which 1,2-difluoroethylene isomer (E and/or Z) was used.It was mentioned that the addition products were obtained as a mixture of diastereomers (Scheme 15).
Tetramethyldiarsine was shown to react with (Z/E)-1,2-difluoroethylene under UV irradiation, yielding the product as a mixture of the racemate and the meso form in high combined yield (90%, Scheme 16) [94].The product was used as a ligand for the preparation of transitional metal carbonyl complexes.
The addition reaction of trichlorofluoromethane (CFC-11) to 1,2-difluoroethylene in the presence of aluminum chloride under pressure was described [51].In this electrophilic reaction, two products were formed in 3:1 ratio (Scheme 17) in a very low yield of 0.4%.
All data reported for the [2 + 2]-cycloaddition reaction of fluorinated ketones and aldehydes [49,100] were indicative of the fact that under photochemical conditions, this reaction is likely to be a stepwise process involving the formation of a biradical intermediate.

Additional author remarks
Other attempts to utilize 1,2-difluoroethylene in reactions with N-, O-, C-nucleophiles carried out in our group were unsuccessful [78], while S-nucleophiles, namely thiophenolates, led to products upon fluorine atom substitution, which were isolated in low yield.Corresponding disulfides were isolated as major products, even when the reaction was carried out under inert atmosphere, suggesting a radical process.

Conclusion
In conclusion, our literature analysis demonstrated that radical processes are most typical for 1,2-difluoroethylene, while examples of electrophilic reactions are scarce, and nucleophilic reactions were not described at all.Nevertheless, the radical reactions are the most powerful instrument for the preparation of new molecules with a CHF-CHF fragment.For instance, the radical addition of hypohalites is a suitable high-yielding approach toward polyfluorinated aliphatic ethers and esters.Photochemical [2 + 2]-cycloaddition with fluorinated aldehydes and ketones gives access to a variety of fluorinated oxygen-containing heterocycles.We hope that this article will help chemists to utilize HFO-1132 and that this olefin will find applications as a useful synthon in organic chemistry.